S313: HEALTH ECONOMIC EVALUATION OF THIRD-LINE INTERVENTIONS FOR TRANSPLANT-INELIGIBLE RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA IN GERMANY
Authors: Melina Sophie Kurte, Ann-Cathrine Siefen, Anna Marie Bauer, Hans Christian Reinhardt, Florian Kron
Journal: HemaSphere (2023)

Background: There is a variety of treatment options for patients with transplant-ineligible relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). One established option is the chemotherapy-based regimen of rituximab, gemcitabine, and oxaliplatin (R-GemOx). Since 2018, the European Medicines Agency has approved several novel targeted therapies for this indication, including CAR T therapies axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel), as well as the antibody-drug conjugate polatuzumab vedotin alongside bendamustine and rituximab (pola-BR) and the anti-CD19 monoclonal antibody tafasitamab in combination with lenalidomide (Tafa-L). Despite promising impacts on clinical outcomes, these interventions are associated with high treatment costs. The resulting economic burden necessitates the performance of cost-effectiveness analyses (CEAs). In Germany, efficiency frontiers (EF) are the recommended approach to conduct CEAs within one indication area. Aims: The objective was to conduct a health economic evaluation of costs and benefits of third-line and beyond (3+L) interventions for transplant-ineligible R/R DLBCL from a healthcare payer´s perspective in Germany. Methods: A systematic literature review was conducted in PubMed to determine the clinical benefit in terms of median overall survival (OS) of the 3+L interventions R-GemOx, axi-cel, liso-cel, tisa-cel, pola-R, and Tafa-L. Where applicable, the most probable mean value of the varying median OS was estimated via bootstrapping. Following the methods of early benefit assessment of medicinal products in Germany, the annual costs of the first year of treatment were determined. Based on the reference year 2022, drug costs and costs for outpatient medical services were calculated. For CAR T treatment, costs for its inpatient administration were added. Results of clinical benefit and treatment costs were graphically summarized in an EF. Results: The systematic literature review resulted in 11 studies. After applying the bootstrap method for interventions with more than one result for median OS (axi-cel, liso-cel, tisa-cel) clinical benefit estimations were 18.69 (months, standard deviation (SD) 3.1), 18.08 (3.2), and 10.02 (1.32), respectively. Results of median OS (months) for interventions with only one result were: 12.0, 9.5, and 15.5 for R-GemOx, pola-BR, and Tafa-L, respectively. Annual treatment costs were calculated for axi-cel, liso-cel, tisa-cel, R-GemOx, pola-BR, and Tafa-L with € 308,393, € 371,393, € 291,393, € 29,080, € 96,200, € 104,541. Drug costs represented the main cost driver, ranging from € 345,000 (liso-cel) to € 26,510 (R-GemOx). Outpatient medical services consisted of physician fees, fees for medication administration, laboratory, and imaging; highest for Tafa-L (€ 3,861), lowest for CAR T treatment (€ 1,330). Inpatient CAR T administration equaled € 25,063. Thus, the EF is formed by R-GemOx, Tafa-L, and axi-cel. Pola-BR and tisa-cel are dominated by R-GemOx respectively Tafa-L. High uncertainty was found for point estimates of liso-cel and axi-cel.Summary/Conclusion: Although the EF approach is currently under discussion, it provides interesting insights into the cost-effectiveness of interventions to guide decision-making for the pricing of new interventions. We found R-GemOx, Tafa-L and axi-cel to be cost-effective, but uncertainty shows that liso-cel could also be part of the EF. For Tafa-L, the highest increase in benefit per euro is obtained, expressed by the steepest slope compared to the previous intervention (R-GemOx). Keywords: DLBCL, CAR-T, Cost effectiveness, Diffuse large B cell lymphoma